Journal
COMMUNICATIONS BIOLOGY
Volume 5, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s42003-022-04041-0
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Funding
- National Natural Science Foundation of China [81670765, 82070841]
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Metabolomics analysis reveals that inosine monophosphate (IMP) promotes myelopoiesis and contributes to severe acute pancreatitis. These findings provide a potential therapeutic target for the control of vascular complications in diabetes.
Metabolomics analysis reveals that inosine monophosphate, a purine metabolite, promotes myelopoiesis and contributes to severe acute pancreatitis in db/db mice. Hyperglycemia-induced myelopoiesis and atherosclerotic progression occur in mice with type I diabetes. However, less is known about the effects of metabolites on myelopoesis in type 2 diabetes. Here, we use fluorescence-activated cell sorting to analyze the proliferation of granulocyte/monocyte progenitors (GMP) in db/db mice. Using targeted metabolomics, we identify an increase in inosine monophosphate (IMP) in GMP cells of 24-week-old mice. We show that IMP treatment stimulates cKit expression, ribosomal S6 activation, GMP proliferation, and Gr-1(+) granulocyte production in vitro. IMP activates pAkt in non-GMP cells. In vivo, using an established murine acute pancreatitis (AP) model, administration of IMP-treated bone marrow cells enhances the severity of AP. This effect is abolished in the presence of a pAkt inhibitor. Targeted metabolomics show that plasma levels of guanosine monophosphate are significantly higher in diabetic patients with AP. These findings provid a potential therapeutic target for the control of vascular complications in diabetes.
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